Escherichia coli Nissle 1917 outer membrane vesicles encapsulating oncolytic virus remodel tumor-associated macrophages and kill prostate cancer cells.

Oncolytic virus OH2 exerts cytotoxic effect on prostate tumor cells. However, when administered via vein injection, OH2 struggles to accumulate effectively within tumors, and its therapeutic efficacy is diminished. Bacterial outer membrane vesicles (OMVs), bilayer membrane structures ranging from 20 to 250 nm in size, can serve not only as carriers for targeted drug delivery to tumors but also activate immune responses via pathogen-associated molecular patterns (PAMPs) within them. In this study, we encapsulated OH2 within OMVs derived from Escherichia coli Nissle 1917 (EcN). We aimed to leverage the protective capacity and tumor-targeting properties of EcN-OMVs to enhance OH2 accumulation within tumors. Concurrently, both the EcN-OMVs and OH2 are anticipated to collaboratively remodel the immunosuppressive tumor microenvironment of prostate cancer, thereby enhancing overall immunotherapeutic efficacy.